{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T04:38:40Z","timestamp":1778474320442,"version":"3.51.4"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017638","name":"Ministry of Health of the Russian Federation","doi-asserted-by":"publisher","award":["#121102500071-6"],"award-info":[{"award-number":["#121102500071-6"]}],"id":[{"id":"10.13039\/501100017638","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC, the number of TBE cases increase annually. There is no specific treatment for the TBEV infection, thus vaccination is the main preventive measure. Despite the existence of several inactivated vaccines currently being licensed, the development of new TBEV vaccines remains a leading priority in countries endemic to this pathogen. Here we report new recombinant virus made by infectious subgenomic amplicon (ISA) approach using TBEV and yellow fever virus vaccine strain (YF17DD-UN) as a genetic backbone. The recombinant virus is capable of effective replication in mammalian cells and induce TBEV-neutralizing antibodies in mice. Unlike the original vector based on the yellow fever vaccine strain, chimeric virus became neuroinvasive in doses of 10<jats:sup>7<\/jats:sup>\u221210<jats:sup>6<\/jats:sup> PFU and can be used as a model of flavivirus neuroinvasiveness, neurotropism and neurovirulence. These properties of hybrid structures are the main factors limiting their practical use as vaccines platforms.<\/jats:p>","DOI":"10.1371\/journal.pone.0284823","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T18:18:10Z","timestamp":1683742690000},"page":"e0284823","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Development and characterization of chimera of yellow fever virus vaccine strain and Tick-Borne encephalitis virus"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7399-7628","authenticated-orcid":true,"given":"Nadezhda","family":"Kuznetsova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7576-2059","authenticated-orcid":true,"given":"Andrei","family":"Siniavin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Butenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Larichev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Kozlova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evgeny","family":"Usachev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Nikiforova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga","family":"Usacheva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey","family":"Shchetinin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrei","family":"Pochtovyi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Shidlovskaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina","family":"Odintsova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizaveta","family":"Belyaeva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksander","family":"Voskoboinikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arina","family":"Bessonova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyudmila","family":"Vasilchenko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina","family":"Karganova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Zlobin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Logunov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Gushchin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Gintsburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"pone.0284823.ref001","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.antiviral.2019.01.014","article-title":"Tick-borne encephalitis in Europe and Russia: Review of pathogenesis, clinical features, therapy, and vaccines","volume":"164","author":"D Ruzek","year":"2019","journal-title":"Antiviral Res"},{"key":"pone.0284823.ref002","unstructured":"Tick-borne encephalitis\u2014Annual Epidemiological Report for 2020. In: European Centre for Disease Prevention and Control [Internet]. 28 Oct 2022 [cited 8 Feb 2023]. Available: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/tick-borne-encephalitis-annual-epidemiological-report-2020."},{"key":"pone.0284823.ref003","doi-asserted-by":"crossref","first-page":"101972","DOI":"10.1016\/j.ttbdis.2022.101972","article-title":"The epidemiology of infectious diseases in Europe in 2020 versus 2017\u20132019 and the rise of tick-borne encephalitis (1995\u20132020)","volume":"13","author":"VA Jenkins","year":"2022","journal-title":"Ticks Tick Borne Dis"},{"key":"pone.0284823.ref004","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1517\/14712598.2012.704908","article-title":"Clinical development of IMOJEV \u00ae\u2014a recombinant Japanese encephalitis chimeric vaccine (JE-CV)","volume":"12","author":"MB Appaiahgari","year":"2012","journal-title":"Expert Opin Biol Ther"},{"key":"pone.0284823.ref005","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1586\/14760584.2016.1123097","article-title":"Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV\u00ae) in children","volume":"15","author":"K Chokephaibulkit","year":"2016","journal-title":"Expert Rev Vaccines"},{"key":"pone.0284823.ref006","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1586\/erv.11.7","article-title":"New Japanese encephalitis vaccines: alternatives to production in mouse brain","volume":"10","author":"SB Halstead","year":"2011","journal-title":"Expert Rev Vaccines"},{"key":"pone.0284823.ref007","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.vaccine.2016.11.062","article-title":"Post-licensure, phase IV, safety study of a live attenuated Japanese encephalitis recombinant vaccine in children in Thailand","volume":"35","author":"T Chotpitayasunondh","year":"2017","journal-title":"Vaccine"},{"key":"pone.0284823.ref008","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1080\/21645515.2019.1658503","article-title":"A review of Dengvaxia\u00ae: development to deployment","volume":"15","author":"SJ Thomas","year":"2019","journal-title":"Hum Vaccin Immunother"},{"key":"pone.0284823.ref009","first-page":"1","article-title":"A recombinant live attenuated tetravalent vaccine for the prevention of dengue","volume":"16","author":"B Guy","year":"2017","journal-title":"Expert Rev Vaccines"},{"key":"pone.0284823.ref010","doi-asserted-by":"crossref","first-page":"12497","DOI":"10.1128\/JVI.78.22.12497-12507.2004","article-title":"ChimeriVax-West Nile virus live-attenuated vaccine: preclinical evaluation of safety, immunogenicity, and efficacy","volume":"78","author":"J Arroyo","year":"2004","journal-title":"J Virol"},{"key":"pone.0284823.ref011","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/infdis\/jiq003","article-title":"Phase II, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Investigate the Immunogenicity and Safety of a West Nile Virus Vaccine in Healthy Adults","author":"R Biedenbender","year":"2011","journal-title":"The Journal of Infectious Diseases"},{"key":"pone.0284823.ref012","doi-asserted-by":"crossref","first-page":"6656","DOI":"10.1016\/j.vaccine.2012.08.063","article-title":"Phase II, dose ranging study of the safety and immunogenicity of single dose West Nile vaccine in healthy adults \u2265 50 years of age","volume":"30","author":"GH Dayan","year":"2012","journal-title":"Vaccine"},{"key":"pone.0284823.ref013","doi-asserted-by":"crossref","first-page":"13206","DOI":"10.1038\/s41598-018-31375-9","article-title":"Chimeric yellow fever 17D-Zika virus (ChimeriVax-Zika) as a live-attenuated Zika virus vaccine","volume":"8","author":"M Giel-Moloney","year":"2018","journal-title":"Sci Rep"},{"key":"pone.0284823.ref014","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/s41541-018-0092-2","article-title":"A yellow fever-Zika chimeric virus vaccine candidate protects against Zika infection and congenital malformations in mice","volume":"3","author":"DB Kum","year":"2018","journal-title":"NPJ Vaccines"},{"key":"pone.0284823.ref015","doi-asserted-by":"crossref","first-page":"8602","DOI":"10.1128\/JVI.79.13.8602-8613.2005","article-title":"Attenuation of recombinant yellow fever 17D viruses expressing foreign protein epitopes at the surface","volume":"79","author":"MC Bonaldo","year":"2005","journal-title":"J Virol"},{"key":"pone.0284823.ref016","doi-asserted-by":"crossref","first-page":"e59347","DOI":"10.1371\/journal.pone.0059347","article-title":"Recombinant yellow fever viruses elicit CD8+ T cell responses and protective immunity against Trypanosoma cruzi","volume":"8","author":"RT Nogueira","year":"2013","journal-title":"PLoS One"},{"key":"pone.0284823.ref017","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1128\/JVI.02255-09","article-title":"Recombinant yellow fever vaccine virus 17D expressing simian immunodeficiency virus SIVmac239 gag induces SIV-specific CD8+ T-cell responses in rhesus macaques","volume":"84","author":"MC Bonaldo","year":"2010","journal-title":"J Virol"},{"key":"pone.0284823.ref018","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.virol.2005.12.001","article-title":"A recombinant Yellow Fever 17D vaccine expressing Lassa virus glycoproteins","volume":"345","author":"PJ Bredenbeek","year":"2006","journal-title":"Virology"},{"key":"pone.0284823.ref019","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/s41586-020-3035-9","article-title":"A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate","volume":"590","author":"L Sanchez-Felipe","year":"2021","journal-title":"Nature"},{"key":"pone.0284823.ref020","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.vaccine.2014.10.004","article-title":"Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk\/benefit assessment","volume":"33","author":"TP Monath","year":"2015","journal-title":"Vaccine"},{"key":"pone.0284823.ref021","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1099\/vir.0.068023-0","article-title":"Single-stranded positive-sense RNA viruses generated in days using infectious subgenomic amplicons","volume":"95","author":"F Aubry","year":"2014","journal-title":"J Gen Virol"},{"key":"pone.0284823.ref022","article-title":"Reverse Genetics of RNA Viruses: ISA-Based Approach to Control Viral Population Diversity without Modifying Virus Phenotype","volume":"11","author":"J-S Driouich","year":"2019","journal-title":"Viruses"},{"key":"pone.0284823.ref023","article-title":"Comparison of chikungunya viruses generated using infectious clone or the Infectious Subgenomic Amplicons (ISA) method in Aedes mosquitoes","volume":"13","author":"SM Ali","year":"2018","journal-title":"PLoS One"},{"key":"pone.0284823.ref024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0159564","article-title":"Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days","volume":"11","author":"L de Fabritus","year":"2016","journal-title":"PLoS One"},{"key":"pone.0284823.ref025","first-page":"2336","article-title":"ESTABLISHMENT OF PLAQUE ASSAY METHOD FOR TITRATING YELLOW FEVER VACCINE","author":"Central Research Institute","year":"2017","journal-title":"International Journal of Advanced Research"},{"key":"pone.0284823.ref026","doi-asserted-by":"crossref","DOI":"10.1016\/j.vaccine.2014.02.046","article-title":"Evaluation of immune response and protective effect of four vaccines against the tick-borne encephalitis virus","volume":"32","author":"OV Morozova","year":"2014","journal-title":"Vaccine"},{"key":"pone.0284823.ref027","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A SIMPLE METHOD OF ESTIMATING FIFTY PER CENT ENDPOINTS12","author":"LJ Reed","year":"1938","journal-title":"American Journal of Epidemiology"},{"key":"pone.0284823.ref028","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.vaccine.2007.12.015","article-title":"Evaluation of the Langat\/dengue 4 chimeric virus as a live attenuated tick-borne encephalitis vaccine for safety and immunogenicity in healthy adult volunteers","volume":"26","author":"PF Wright","year":"2008","journal-title":"Vaccine"},{"key":"pone.0284823.ref029","doi-asserted-by":"crossref","first-page":"3095","DOI":"10.1128\/JVI.73.4.3095-3101.1999","article-title":"Yellow fever\/Japanese encephalitis chimeric viruses: construction and biological properties","volume":"73","author":"TJ Chambers","year":"1999","journal-title":"J Virol"},{"key":"pone.0284823.ref030","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1073\/pnas.95.4.1746","article-title":"Attenuation of the Langat tick-borne flavivirus by chimerization with mosquito-borne flavivirus dengue type 4","volume":"95","author":"AG Pletnev","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0284823.ref031","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1073\/pnas.022652799","article-title":"West Nile virus\/dengue type 4 virus chimeras that are reduced in neurovirulence and peripheral virulence without loss of immunogenicity or protective efficacy","volume":"99","author":"AG Pletnev","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0284823.ref032","doi-asserted-by":"crossref","first-page":"4307","DOI":"10.1016\/S0264-410X(03)00488-2","article-title":"Substitution of the structural genes of dengue virus type 4 with those of type 2 results in chimeric vaccine candidates which are attenuated for mosquitoes, mice, and rhesus monkeys","volume":"21","author":"SS Whitehead","year":"2003","journal-title":"Vaccine"},{"key":"pone.0284823.ref033","doi-asserted-by":"crossref","first-page":"405","DOI":"10.4269\/ajtmh.2001.65.405","article-title":"Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3\u2019-untranslated region","volume":"65","author":"AP Durbin","year":"2001","journal-title":"Am J Trop Med Hyg"},{"key":"pone.0284823.ref034","doi-asserted-by":"crossref","first-page":"3020","DOI":"10.1128\/JVI.74.7.3020-3028.2000","article-title":"Chimeric dengue type 2 (vaccine strain PDK-53)\/dengue type 1 virus as a potential candidate dengue type 1 virus vaccine","volume":"74","author":"CY Huang","year":"2000","journal-title":"J Virol"},{"key":"pone.0284823.ref035","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1006\/viro.2000.0426","article-title":"Chimeric Langat\/Dengue viruses protect mice from heterologous challenge with the highly virulent strains of tick-borne encephalitis virus","volume":"274","author":"AG Pletnev","year":"2000","journal-title":"Virology"},{"key":"pone.0284823.ref036","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.vaccine.2013.12.050","article-title":"Recombinant chimeric Japanese encephalitis virus\/tick-borne encephalitis virus is attenuated and protective in mice","volume":"32","author":"H-J Wang","year":"2014","journal-title":"Vaccine"},{"key":"pone.0284823.ref037","doi-asserted-by":"crossref","first-page":"10532","DOI":"10.1073\/pnas.89.21.10532","article-title":"Construction and characterization of chimeric tick-borne encephalitis\/dengue type 4 viruses","volume":"89","author":"AG Pletnev","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0284823.ref038","article-title":"Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise","volume":"8","author":"M Kubinski","year":"2020","journal-title":"Vaccines (Basel)"},{"key":"pone.0284823.ref039","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.vaccine.2005.07.067","article-title":"Comparison of live and inactivated tick-borne encephalitis virus vaccines for safety, immunogenicity and efficacy in rhesus monkeys","volume":"24","author":"AA Rumyantsev","year":"2006","journal-title":"Vaccine"},{"key":"pone.0284823.ref040","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1086\/649916","article-title":"A novel tetravalent dengue vaccine is well tolerated and immunogenic against all 4 serotypes in flavivirus-naive adults","volume":"201","author":"D Morrison","year":"2010","journal-title":"J Infect Dis"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0284823","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T18:18:47Z","timestamp":1683742727000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0284823"}},"subtitle":[],"editor":[{"given":"G\u00e1bor","family":"Kemenesi","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0284823","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,10]]}}}